EU/3/19/2142: Orphan designation for the treatment of epidermolysis bullosa

Epidermolysis bullosa is a group of inherited diseases in which the skin is very fragile and forms severe blisters after even minor friction (rubbing) or injury. In most cases, symptoms of epidermolysis bullosa appear from birth, but for some forms, symptoms may not occur until adulthood. The diseases are caused by mutations (changes) in the genes responsible for the production of certain proteins that make the skin strong and elastic, such as collagen or keratins.

Epidermolysis bullosa is a long-term debilitating and life-threatening condition because the severe blistering and associated scarring and deformities result in poor quality of life and may reduce life expectancy.

At the time of designation, Epidermolysis bullosa affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 26,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

At the time of designation, no satisfactory methods were authorised in the EU to treat epidermolysis bullosa. Good personal hygiene and skincare were recommended to help blisters heal, to avoid infections and to protect the skin from damage. Painkillers were also used. Surgery was sometimes necessary for complications such as deformed hands or skin cancer.

In patients with epidermolysis bullosa, the severe skin blisters lead to the formation of scars on the skin. Losartan is expected to block the action of a protein called TGFβ which is involved in the processes that cause scarring and thereby reduces the symptoms of the disease.

The effects of losartan have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with losartan in patients with epidermolysis bullosa was ongoing.

At the time of submission, losartan tablets were widely used for the treatment of high blood pressure.

At the time of submission, losartan was not authorised anywhere in the EU for epidermolysis bullosa or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 January 2019 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.